Cancers

Background/Objectives: Adenocarcinomas of the esophagogastric junction and stomach present clinical entities with significant cancer-related morbidity and mortality, often requiring multimodal treatments. Preoperative chemotherapy, mainly the FLOT regimen, is increasingly being utilized in the neoadjuvant setting for the treatment of these malignancies, with varying degrees of tumor response. Methods: We conducted a retrospective, single-institution review on 75 patients operated on for adenocarcinoma of the esophagogastric junction and stomach after neoadjuvant FLOT. We investigated whether tumor response correlates with disease response in lymph nodes examined on surgical specimens. We also investigated the role of tumor-infiltrating lymphocytes (TILs) in correlation with primary tumor response and disease response in lymph nodes on pathological specimens. Results: Our results suggest that TILs correlate in a differential manner with regards to primary tumors versus lymph nodes, thus suggesting that there are different biologic processes in place. Conclusions: Our results provide unique evidence on tumor-infiltrating lymphocytes in the adenocarcinoma histology of the esophagogastric junction and stomach and might be important for further studies.

Approximately 15–20% of cancers are caused by viruses. Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8), is an oncogenic virus that is the etiologic agent of not only Kaposi sarcoma but also the lymphoproliferative disorders, primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). KSHV can infect a broad tropism of cells, including B lymphocytes, wherein KSHV encodes specific viral proteins that can transform the cell. KSHV infection precedes the progression of PEL and MCD. KSHV establishes lifelong infection and has two phases of its lifecycle: latent and lytic. During the latent phase, viral genomes are maintained episomally with limited gene expression. Upon sporadic reactivation, the virus enters its replicative lytic phase to produce infectious virions. KSHV relies on its viral products to modulate host factors to evade immune detection or to co-opt their function for KSHV persistence. These manipulations dysregulate normal cell pathways to ensure cell survival and inhibit antiviral immune responses, which in turn, contribute to KSHV-associated malignancies. Here, we highlight the known molecular mechanisms of KSHV that promote lymphomagenesis and how these findings identify potential therapeutic targets for KSHV-associated lymphomas.

Spine metastases (SMs) are common, arising in 70% of the cases of the most prevalent malignancies in males (prostate cancer) and females (breast cancer). Stereotactic body radiotherapy, or SBRT, has been incorporated into clinical treatment algorithms over the past decade. SBRT has shown promising rates of local control for oligometastatic spinal lesions with low radiation dose to adjacent critical tissues, particularly the spinal cord. Imaging is critically important in SBRT planning, guidance, and response monitoring. This paper reviews the roles of imaging in spine SBRT, including conventional and advanced imaging approaches for SM detection, treatment planning, and post-SBRT follow-up.

Background: Cancer remains a leading cause of death worldwide. Progress in its effective treatment has been hampered by challenges in personalized therapy, particularly in patients with comorbid conditions. The integration of artificial intelligence (AI) into patient profiling offers a promising approach to enhancing individualized anticancer therapy. Objective: This narrative review explores the role of AI in refining anticancer therapy through personalized profiling, with a specific focus on cancer patients with comorbid migraine. Methods: A comprehensive literature search was conducted across multiple databases, including PubMed, Scopus, and Google Scholar. Studies were selected based on their relevance to AI applications in oncology and migraine management, with a focus on personalized medicine and predictive modeling. Key themes were synthesized to provide an overview of recent developments, challenges, and emerging directions. Results: AI technologies, such as machine learning (ML), deep learning (DL), and natural language processing (NLP), have become instrumental in the discovery of genetic and molecular biomarkers of cancer and migraine. These technologies also enable predictive analytics for assessing the impact of migraine on cancer therapy in comorbid cases, predicting outcomes and provide clinical decision support systems (CDSS) for real-time treatment adjustments. Conclusions: AI holds significant potential to improve the precision and effectiveness of the management and therapy of cancer patients with comorbid migraine. Nevertheless, challenges remain over data integration, clinical validation, and ethical consideration, which must be addressed to appreciate the full potential for the approach outlined herein.

Background: The identification of reliable prognostic biomarkers is crucial for optimizing cancer treatment strategies, especially in the era of personalized medicine. This systematic review and meta-analysis evaluate the prognostic significance of the neutrophil-to-eosinophil ratio (NER) in various cancer types, with a focus on its association with overall survival (OS) and progression-free survival (PFS). Methods: We conducted a systematic literature search across PubMed, Scopus, and Web of Science databases for studies published up to 28 July 2024. We performed the meta-analyses with the generic inverse variance method with a random effects model and reported hazard ratios (HR) with 95% confidence intervals (CI). Results: The comprehensive literature search identified 10 studies comprising 2351 patients. Pooled analyses demonstrated that elevated pretreatment NER levels were significantly correlated with poorer OS (HR: 1.74, 95% CI: 1.28–2.36, p < 0.001) and PFS (HR: 1.53, 95% CI: 1.21–1.95, p < 0.001). Subgroup analyses confirmed a consistent adverse association between high NER and OS across various tumor types and geographic locations, although results from studies conducted in the Far East did not reach statistical significance. Conclusions: This meta-analysis demonstrates that elevated NER is associated with poorer OS and PFS in cancer patients, suggesting its potential utility as a non-invasive prognostic marker. Further validation in large, prospective studies is warranted to establish NER’s role in guiding personalized treatment strategies across diverse oncologic contexts.

Minerals constitute only 5% of the typical human diet but are vital for health and functionality. Copper, a trace element, is absorbed by the human gut at 30–40% from diets typical of industrialized countries. The liver produces metallothioneins, which store copper. Copper is crucial for mitochondrial respiration, pigmentation, iron transport, antioxidant defense, hormone production, and extracellular matrix biosynthesis. Copper deficiency, often caused by mutations in the ATP7A gene, results in Menkes disease, an X-linked recessive disorder. On the contrary, Wilson disease is characterized by toxic copper accumulation. Cuproptosis, a unique form of cell death regulated by copper, is a subtype of necrosis induced by enhanced mitochondrial metabolism and intracellular copper accumulation. This process can reduce the malignant potential of tumor cells by inhibiting glucose metabolism. Therapeutically, copper and its complexes have shown efficacy in malignancy treatments. The disruption of copper homeostasis and excessive cuproplasia are significant in colorectal cancer development and metastasis. Therefore, manipulating copper status presents a potential therapeutic target for colorectal cancer, using copper chelators to inhibit copper formation or copper ion carriers to promote cuproptosis. This review highlights the role of copper in human physiology and pathology, emphasizing its impact on colorectal cancer and potential therapeutic strategies. Future AI-based approaches are anticipated to accelerate the development of new compounds targeting cuproptosis and copper disruption in colorectal cancer.

The purpose of this article is to provide a literature review of the epigenetic understanding of conjunctival melanoma (CM), with a primary focus on current gaps in knowledge and future directions in research. CM is a rare aggressive cancer that predominantly affects older adults. Local recurrences and distant metastases commonly occur in CM patients; however, their prediction and management remain challenging. Hence, there is currently an unmet need for useful biomarkers and more effective treatments to improve the clinical outcomes of these patients. Like other cancers, CM occurrence and prognosis are believed to be influenced by multiple genetic and epigenetic factors that contribute to tumor development/progression/recurrence/spread, immune evasion, and primary/acquired resistance to therapies. Epigenetic alterations may involve changes in chromatin conformation/accessibility, post-translational histone modifications or the use of histone variants, changes in DNA methylation, alterations in levels/functions of short (small) or long non-coding RNAs (ncRNAs), or RNA modifications. While recent years have witnessed a rapid increase in available epigenetic technologies and epigenetic modulation-based treatment options, which has enabled the development/implementation of various epi-drugs in the cancer field, the epigenetic understanding of CM remains limited due to a relatively small number of epigenetic studies published to date. These studies primarily investigated DNA methylation, ncRNA (e.g., miRNA or circRNA) expression, or RNA methylation. While these initial epigenetic investigations have revealed some potential biomarkers and/or therapeutic targets, they had various limitations, and their findings warrant replication in independent and larger studies/samples. In summary, an in-depth understanding of CM epigenetics remains largely incomplete but essential for advancing our molecular knowledge and improving clinical management/outcomes of this aggressive disease.

Prostate cancer progression is significantly affected by its tumor microenvironment, in which mesenchymal cells play a crucial role. Stromal cells are modified by cancer mutations, response to androgens, and lineage plasticity, and in turn, engage with epithelial tumor cells via a complex array of signaling pathways and ligand–receptor interactions, ultimately affecting tumor growth, immune interaction, and response to therapy. The metabolic rewiring and interplay in the microenvironment play an additional role in affecting the growth and progression of prostate cancer. Finally, therapeutic strategies and novel clinical trials with agents that target the stromal microenvironment or disrupt the interaction between cellular compartments are described. This review underscores cancer-associated fibroblasts as essential contributors to prostate cancer biology, emphasizing their potential as prognostic indicators and therapeutic targets.

Brain and leptomeningeal metastases are complications of breast cancer with high rates of morbidity and mortality and have an estimated incidence of up to 30%. While National Comprehensive Cancer Network (NCCN) guidelines recommend screening for central nervous system metastasis in other neurotropic cancers such as non-small cell lung cancer, there are no such recommendations for asymptomatic breast cancer patients at any stage of disease. This review highlights ongoing studies into screening and diagnostics for breast cancer with brain and leptomeningeal metastasis (BCBLM) as they relate to patient outcomes and prognostication. These include imaging methods such as MRI with novel contrast agents with or without PET/CT, as well as ‘liquid biopsy’ testing of the cerebrospinal fluid and serum to analyze circulating tumor cells, genomic material, proteins, and metabolites. Given recent advances in radiation, neurosurgery, and systemic treatments for BCBLM, screening for CNS involvement should be considered in patients with advanced breast cancer as it may impact treatment decisions and overall survival.

Background/Objectives: With breast cancer (BC) survival improving due to optimized therapy, enhancing quality of life has become increasingly important. Both diagnosis and treatment, with their potential side effects, pose risks to mental well-being. Our study aimed to analyze the incidence and potential risk factors for mental disorders in BC patients. Methods: This retrospective analysis used claims data from AOK Baden-Wuerttemberg, including 11,553 BC patients diagnosed via ICD code C50 between 2010 and 2020 and 31,944 age-matched controls. Patients with mental disorders in the 12 months prior to diagnosis were excluded. Mental disorders were categorized into eight groups based on ICD codes: anxiety, obsessive compulsive disorder, adjustment disorder, dissociative disorder, hypochondriac disorder, affective disorder, mania, and other neuroses. Results: Mental disorders were significantly more common in BC patients than in controls (64.2% vs. 38.1%, p < 0.01, OR 2.91, 95%CI [2.79, 3.04]). In particular, hypochondriac, anxiety, affective, and adjustment disorders occurred significantly more often in BC patients. No differences were found for mania, bipolar disease, other neuroses, obsessive compulsive-, or dissociative disorders. Furthermore, endocrine therapy was associated with psychological comorbidities (OR 1.69, p < 0.001, 95%CI [1.53, 1.86]), while primarily metastasized patients (stage C) had a lower risk than adjuvant patients in stage A (OR 0.55, p < 0.0001, 95%CI [0.49, 0.61]). Regarding surgical treatment, mastectomy patients showed lower rates of mental illnesses (61.2%) than those with breast-conserving treatment (71.6%), or especially breast reconstruction (78.4%, p < 0.01). Breast reconstruction was also associated with more hypochondriac (p < 0.01) and adjustment disorders (p < 0.01). Conclusions: So, BC patients experience significantly more mental disorders than controls, particularly when treated with endocrine therapy and breast reconstructive surgery.